Package Insert (Instructions for Use) - For use under Emergency Use Authorization only For in vitro diagnostic use only For prescription use only ...
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For use under Emergency Use Authorization only
For in vitro diagnostic use only
For prescription use only
CLIA complexity: MODERATE and HIGH
Rapid Diagnostic Test for the Detection of SARS-CoV-2 IgM/IgG Ab
Package Insert
(Instructions for Use)
RCLM-02571
CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
Table of Contents
Intended Use ........................................................................................................................................... 3
Summary and Explanation of the Test ............................................................................................. 3
Principles of the Test ............................................................................................................................ 4
Reagents and Materials Provided...................................................................................................... 5
Warnings and Precautions .................................................................................................................. 5
Storage and Stability ............................................................................................................................. 6
Quality Control ........................................................................................................................................ 6
Specimen Type ....................................................................................................................................... 7
Limitations ............................................................................................................................................. 11
Conditions of Authorization for Laboratories .............................................................................. 12
Performance Characteristics ............................................................................................................ 13
IFU-RCLM71-E / Rev. A ACCESS BIO, INC. Page 2 of 19RCLM-02571
CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
For in vitro diagnostic use only
For prescription use only
For Emergency Use Authorization only
CLIA complexity: MODERATE and HIGH
Intended Use
The CareStart™ COVID-19 IgM/IgG is an immunochromatographic lateral flow assay intended
for the qualitative detection and differentiation of Immunoglobulin M (IgM) and Immunoglobulin
G (IgG) antibodies to SARS-CoV-2 in human serum, plasma (sodium citrate, sodium heparin,
or dipotassium EDTA), and venous whole blood (sodium citrate, sodium heparin, or
dipotassium EDTA). The CareStart™ COVID-19 IgM/IgG is intended for use as an aid in
identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or
prior infection. At this time, it is unknown for how long antibodies persist following infection and
if the presence of antibodies confers protective immunity. The CareStart™ COVID-19 IgM/IgG
should not be used to diagnose acute SARS-CoV-2 infection. This testing is limited to
laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA),
42 U.S.C. §263a, that meet requirements to perform moderate or high complexity tests.
Results are for the detection of SARS-CoV-2 antibodies. IgM and IgG antibodies to SARS-
CoV-2 are generally detectable in blood several days after initial infection, although the duration
of time antibodies are present post-infection is not well characterized. Individuals may have
detectable virus present for several weeks following seroconversion.
Laboratories within the United States and its territories are required to report all positive results
to the appropriate public health authorities.
The sensitivity of CareStart™ COVID-19 IgM/IgG early after infection is unknown. Negative
results do not preclude acute SARS-CoV-2 infection. If acute infection is suspected, direct
testing for SARS-CoV-2 is necessary.
False positive results for CareStart™ COVID-19 IgM/IgG may occur due to cross-reactivity
from pre-existing antibodies or other possible causes. Due to the risk of false positive results,
confirmation of positive results should be considered using a second, different SARS-CoV-2
IgG or IgM assay.
The CareStart™ COVID-19 IgM/IgG is only for use under the Food and Drug Administration’s
Emergency Use Authorization.
Summary and Explanation of the Test
Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to
person. This antibody test is intended for use as an aid in identifying individuals with an
IFU-RCLM71-E / Rev. A ACCESS BIO, INC. Page 3 of 19RCLM-02571 CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab adaptive immune response to SARS-CoV-2, the virus that causes COVID-19, indicating recent or prior infection, by detecting antibodies to SARS-CoV-2 in human blood specimens. Although not everyone who is infected will develop an antibody response, appropriately validated serology tests, when used broadly, can be useful in understanding how many people have developed an adaptive immune response to the virus and how far the pandemic has progressed. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity. Principles of the Test The CareStart™ COVID-19 IgM/IgG test is an immunochromatographic assay for the detection and differentiation of SARS-CoV-2 IgM and/or IgG antibodies in human blood specimens. Control antibody, anti-human IgG, and streptavidin (test line for IgM) are immobilized onto a nitrocellulose membrane to form three distinct lines, the control line, the IgG test line, and the IgM test line. The nitrocellulose membrane is attached onto a plastic backing card and combined with the other reagents and pads to construct a test strip. The test strip is encased inside a plastic device. Blood samples, including human serum, plasma (sodium citrate, sodium heparin, or dipotassium EDTA), and venous whole blood (sodium citrate, sodium heparin, or dipotassium EDTA), are added to the sample well of the test device to initiate a test. The sample specimens migrate sequentially through filter pad, conjugate pad, nitrocellulose membrane, and absorbent pad. SARS-CoV-2 antibodies in sample specimens interact with the recombinant SARS-CoV-2 antigen (SARS-CoV-2 nucleocapsid and spike protein S1 RBD) that is conjugated to colloidal gold nanobeads and biotin-conjugated anti-human antibodies to form an immune complex while it migrates through the conjugate pad. IgM antibodies react with the gold-conjugated SARS-CoV-2 antigen and biotin-conjugated anti-human IgM. IgG antibodies only react with the gold-conjugated SARS-CoV-2 antigen. The immune complexes migrate through the nitrocellulose membrane and bind to each respective test line. The IgM immune complexes bind to the streptavidin region (IgM test line, “M”) on the membrane to generate a purple-colored line to indicate a positive IgM result. The IgG immune complexes bind to the anti-human IgG region (IgG test line, “G”) on the membrane to generate a purple-colored line to indicate a positive IgG result. The gold-conjugated chicken IgY migrates through the membrane and binds to the control antibody (anti-chicken IgY) in the control region to generate a red-colored line (control line, “C”). The test results should be interpreted 10 minutes after addition of buffer to the sample well. The test results should not be interpreted after 15 minutes. The color intensity in the test region will vary. Any faint colored line(s) in the test region(s) should be considered as positive. The presence of two lines marked by “C” and “G” indicates a SARS-CoV-2 IgG positive result. The presence of two lines marked by “C” and “M”, indicates a SARS-CoV-2 IgM positive result. The presence of three lines “C”, “G,” and “M”, indicates positive results for both SARS-CoV-2 IFU-RCLM71-E / Rev. A ACCESS BIO, INC. Page 4 of 19
RCLM-02571
CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
IgG and IgM. The appearance of only the control line “C” indicates negative. If the control line
does not appear, regardless of the presence of “G” or “M” test lines, the test result is not valid.
With an invalid result, it is recommended to repeat the test using a new, unopened device
following the instructions.
Reagents and Materials Provided
Contents Name Quantity (in a kit) Description
Foil pouched test device containing one test strip
Test device 25 each
which is encased on plastic device cassette.
Assay buffer bottle 1 each Na2CO3, < 0.1% sodium azide as a preservative.
Blood transfer pipette 25 each For blood transfer.
Package insert 1 each Instructions for use
* Materials not supplied
20 µl micropipette Timer Pair of gloves
External positive and negative controls (available for purchase separately)
Warnings and Precautions
For prescription and in vitro diagnostic use only. For Use under an Emergency Use Authorization
Only.
This test has not been FDA cleared or approved; the test has been authorized by FDA under an
Emergency Use Authorization (EUA) for use by laboratories certified under the Clinical Laboratory
Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, that meet requirements to perform
moderate or high complexity tests.
This test has been authorized only for the presence of IgM and IgG antibodies against SARS-CoV-
2, not for any other viruses or pathogens.
This test is only authorized for the duration of the declaration that circumstances exist justifying the
authorization of emergency use of in vitro diagnostic tests for detection and/or diagnosis of COVID-
19 under Section 564(b)(1) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 360bbb-
3(b)(1), unless the authorization is terminated or revoked sooner.
As with all diagnostic tests, all results must be interpreted together with other clinical information
available to the physician.
Immediately use after opening the test device in the pouch.
Immediately add the assay buffer to the test device after the specimen is applied.
In order to obtain accurate results, the test must follow this package insert.
Do not interpret the test result before 10 minutes and after 15 minutes following the addition of
buffer to the sample well.
Do not use if the test device package is damaged.
Do not use the kit contents beyond the expiration date.
Do not eat, drink, or smoke in the area where the specimens and kit contents are handled.
Use appropriate precautions in the collection, handling, storage, and disposal of patient samples
and used kit contents.
Dispose of used contents as biohazardous wastes in accordance with federal, state, and local
requirements.
Nitrile or latex gloves should be worn when performing this test.
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CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
If the assay buffer contacts the skin or eye, flush with copious amounts of water.
Handle all specimens as though they contain infectious agents.
Adding additional blood sample volume to the sample well may cause false positive or invalid
results.
Observe established precautions against microbiological hazards throughout the procedure and
follow the standard procedures for proper disposal of specimens.
Reagents contain sodium azide, which is harmful if inhaled, swallowed, or exposed to skin.
Contact with acids produces a very toxic gas. If there is contact with skin, wash immediately with
plenty of water. Sodium azide may react with lead and copper plumbing to form highly explosive
metal azides. On disposal, flush with a large volume of water to prevent azide build-up.
Do not interchange kit contents from different lots.
Do not re-use any contents in the kit (e.g., blood transfer pipette, test cassette) as they are single-
use only.
Storage and Stability
• Store the test kit as packaged between 1 ~ 30°C.
• The reagents and materials in the CareStart™ COVID-19 IgM/IgG are stable until the
expiration date printed on the outer packaging. Do not use beyond the expiration date.
• The test device must remain in the sealed pouch until use.
• Do not freeze any contents of the kit.
Quality Control
Internal Quality Control: The CareStart™ COVID-19 IgM/IgG contains a built-in internal
procedural control in the test device. A red-colored line appearing in the control region “C” is
designed as an internal procedural control. The appearance of the procedural control line
indicates that sufficient flow has occurred, and the functional integrity of the test device has
been maintained. If the procedural control line does not develop in 10 minutes, the test result
is considered invalid and retesting with a new device is recommended. If the internal procedural
control line is still absent in the retest, please contact the manufacturer or distributor.
External Control: It is recommended to follow the laboratory regulations or quality control
procedures to perform external controls in CareStart™ COVID-19 IgM/IgG. Controls are
available through Access Bio under catalog number: # SCLM-02571 or SCLM-10071.
NOTE: The external controls are available for separate purchase.
• Positive External Control: Mixture of human chimeric SARS-CoV-2 IgM and IgG
spike S1 antibodies in heat inactivated SARS-CoV-2 antibody negative confirmed
serum.
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CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
• Negative External control: Heat inactivated SARS-CoV-2 antibody negative
confirmed serum.
Specimen Type
Acceptable specimen types for testing with the CareStart™ COVID-19 IgM/IgG are human
serum, plasma (sodium citrate, sodium heparin, or dipotassium EDTA), and venous whole
blood (sodium citrate, sodium heparin, or dipotassium EDTA). Proper specimen collection
methods must be followed. Inadequate specimen collection and/or improper specimen
handling may yield false results; therefore, specimen collection requires specific training and
guidance due to the importance of specimen quality to obtain accurate test results.
Specimen Collection and Handling Procedures
Procedural Notes
• Collect the specimen wearing safety gloves to avoid contact and contamination.
• Venous Whole Blood:
Draw venous whole blood following the general laboratory procedures by a trained operator.
Collect the blood sample in a commercially available blood collection tube containing
anticoagulants including sodium citrate, sodium heparin, or dipotassium EDTA. Swirl the tube
gently as needed.
• Serum:
Collect venous whole blood into a container NOT containing anticoagulants. Wait for the
blood clot and separate the serum by centrifugation.
• Plasma:
Collect venous whole blood into a container containing anticoagulants (sodium citrate,
sodium heparin, or dipotassium EDTA). Separate the plasma by centrifugation.
1. The CareStart™ COVID-19 IgM/IgG can be performed using human serum, plasma
(sodium citrate, sodium heparin, or dipotassium EDTA), and venous whole blood (sodium
citrate, sodium heparin, or dipotassium EDTA).
2. Separate serum or plasma from blood as soon as possible to avoid hemolysis. Use only
clear, non-hemolyzed specimens.
3. Testing should be performed immediately after specimen collection. Do not leave the
serum and plasma specimens at room temperature beyond 8 hours. Serum and plasma
specimens may be stored at 2-8°C for up to 48 hours. For long term storage, serum and
plasma specimens should be kept below -20°C for up to one month. It is recommended
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CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
to test whole blood specimens immediately after blood collection.
4. Bring specimens to room temperature prior to testing. Frozen specimens must be
completely thawed and mixed well prior to testing. Specimens cannot be frozen and
thawed more than once.
5. If specimens are to be shipped, they should be packed in compliance with local
regulations covering the transportation of etiologic agents.
Test Procedures
Procedural Notes
• Allow test devices, reagents, and specimens to equilibrate up to room temperature
(15~30°C) prior to testing.
• Remove the CareStart™ COVID-19 IgM/IgG test device from its foil pouch immediately
before testing.
• The CareStart™ COVID-19 IgM/IgG kit IS AUTHORIZED to be used only with human
serum, plasma (sodium citrate, sodium heparin, or dipotassium EDTA), and venous whole
blood (sodium citrate, sodium heparin, or dipotassium EDTA) specimens.
• Use only provided blood transfer pipette or micropipette for sample loading to the test
device.
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CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
1. Place a device on a clean, flat surface after removing it from the pouch. Write the patient’s ID
on the device if required.
2. Transfer venous whole blood, serum or plasma sample:
a) using a provided blood transfer pipette:
Press the top part of the provided blood transfer pipette and touch the sample by the pipette tip
while pressing the pipette. Releasing the press slowly to fill the pipette with sample up to the
blue marked line (approximately 10 µl). Add the blood sample to the sample well “S” of the
test device by pressing the top part of the blood transfer pipette.
NOTE: Excessive blood may cause false positive or invalid test results.
b) using a micropipette:
Transfer 10 µl of the venous whole blood, serum or plasma sample to the sample well “S”
of the test device using a micropipette.
3. Open the cap and invert the assay buffer 4. Start a timer. Read the result at 10 minutes.
bottle and hold vertically above the sample The test results should not be read earlier
well. Squeeze the bottle gently to add one than 10 minutes. Test results should not be
(1) drop of the assay buffer solution to the read after 15 minutes.
sample well “S” immediately after sample
loading.
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CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
Interpretation of Results
NOTE: The test results should be read and interpreted not earlier than 10 minutes after
the sample application and the reading and interpretation of the results should not
exceed 15 minutes. The test results should not be interpreted using any instruments.
IgM Positive: two distinct lines appear.
One red-colored line next to “C” and one purple-colored line next to
“M” indicates SARS-CoV-2 IgM positive result.
IgG Positive: two distinct lines appear.
One red-colored line next to “C” and one purple-colored line next to
“G” indicates SARS-CoV-2 IgG positive result.
IgM/IgG Positive: three distinct lines appear.
One red-colored line next to “C”, one purple-colored line next to “M”,
and one purple-colored line next to “G” indicates SARS-CoV-2 IgM
and IgG positive result.
Result with faint colored line(s):
The color intensity in the test region will vary. Any faint
colored line(s) in the test region(s) should be considered
as positive.
Negative:
Only one line next to “C” indicates a negative result.
Invalid: no control line appears.
If the control line “C” is not visible, the result is
invalid. Re-run the test using a new test
device. If the same invalid result persists,
contact the manufacturer or distributor before
continuing to test samples.
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CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
Limitations
1. For use under an Emergency Use Authorization only.
2. Use of the CareStart™ COVID-19 IgM/IgG is limited to laboratory personnel who have been
trained. Not for home use or point of care (POC) use.
3. The test is limited to the qualitative detection of anti-COVID-19 antibody levels in human
serum and ACD plasma samples and does not indicate the quantity of the antibodies. The
intensity of the test line does not necessarily correlate to SARS-CoV-2 antibody titer in the
specimen.
4. The test results should be interpreted 10 minutes after starting the test. The test results
should not be interpreted after 15 minutes.
5. This test can only be used for the analysis of human serum, plasma (sodium citrate, sodium
heparin, or dipotassium EDTA), and venous whole blood (sodium citrate, sodium heparin, or
dipotassium EDTA) samples. Do not use the CareStart™ COVID-19 IgM/IgG with fingerstick
(capillary) whole blood samples.
6. Negative results do not preclude SARS-CoV2 infection and should not be used as the sole
basis for patient management decisions. IgM antibodies may not be detected in the first
several days of infection; the sensitivity of the Rapid COVID-19 IgM/IgG Combo Test Kit
early after infection is unknown. False positive results for IgM and IgG antibodies may
occur due to cross-reactivity from pre-existing antibodies or other possible causes.
7. A negative result can occur if the quantity of antibodies for the SARS-CoV-2 virus present
in the specimen is below the detection limit of the assay, or if the virus has undergone
minor amino acid mutation(s) in the epitope recognized by the antibody used in the test.
8. The test may have lower sensitivity for IgG and IgM detection in symptomatic individuals
prior to 15 days since symptom onset.
9. Direct testing with a molecular diagnostic test should be performed to evaluate for acute
SARS-CoV-2 infection in symptomatic individuals.
10. Results from antibody testing should not be used to diagnose or exclude acute SARS-CoV-
2 infection or to determine infection status.
11. It is unknown for how long antibodies persist following infection and if the presence of
antibodies confers protective immunity.
12. Positive results may not indicate previous SARS-CoV-2 infection. Consider other information
including clinical history and local disease prevalence, in assessing the need for an
alternative serology test to confirm an adaptive immune response. Positive results may be
due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as
coronavirus HKU1, NL63, OC43, or 229E.
13. This test will only indicate the presence of SARS-CoV-2 IgM and/or IgG antibodies in the
specimen.
14. The detection of SARS-CoV-2 IgM/IgG antibodies is dependent upon proper specimen
collection, handling, storage, and preparation. Failure to observe proper procedures in any
one of these steps can lead to incorrect results.
15. This device has been evaluated for use with human specimen material only.
IFU-RCLM71-E / Rev. A ACCESS BIO, INC. Page 11 of 19RCLM-02571 CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab 16. This test cannot rule out diseases caused by other bacterial or viral pathogens. 17. This device should not be used for the screening of donated blood. Conditions of Authorization for Laboratories The CareStart™ COVID-19 IgM/IgG Letter of Authorization, along with the authorized Fact Sheet for Healthcare Providers, the authorized Fact Sheet for Patients, and other authorized labeling are available on the FDA website: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use- authorizations-medical-devices/vitro-diagnostics-euas Authorized Laboratories using the CareStart™ COVID-19 IgM/IgG (“your product” in the conditions below), must adhere to the Conditions of Authorization indicated in the Letter of Authorization are listed below: 1. Authorized laboratoriesa using the CareStart™ COVID-19 IgM/IgG will include with test result reports, all authorized Fact Sheets. Under exigent circumstances, other appropriate methods for disseminating these Fact Sheets may be used, which may include mass media. 2. Authorized laboratories using the CareStart™ COVID-19 IgM/IgG will use your product as outlined in the Instructions for Use. Deviations from the authorized procedures, including the authorized clinical specimen types, authorized control materials, authorized other ancillary reagents and authorized materials required to use the CareStart™ COVID-19 IgM/IgG are not permitted. 3. Authorized laboratories that receive the CareStart™ COVID-19 IgM/IgG will notify the relevant public health authorities of their intent to run your product prior to initiating testing. 4. Authorized laboratories using the CareStart™ COVID-19 IgM/IgG will have a process in place for reporting test results to healthcare providers and relevant public health authorities, as appropriate. 5. Authorized laboratories will collect information on the performance of the CareStart™ COVID-19 IgM/IgG and report to Division of Microbiology Devices (DMD)/Office of Health Technology7 (OHT7)-(Office of In Vitro Diagnostics and Radiological Health (OIR)/Office of Product Evaluation and Quality (OPEQ)/Center for Devices and Radiological Health (CDRH) (via email: CDRH EUA Reporting@fda.hhs.gov) and Access Bio, Inc. Technical Support (via email: TShelp@accessbio.net) any suspected occurrence of false positive or false negative results and significant deviations from the established performance characteristics of the assay of which they become aware. 6. All laboratory personnel using the CareStart™ COVID-19 IgM/IgG must be appropriately trained in immunochromatographic techniques and use appropriate laboratory and personal protective equipment when handling this kit, and use the CareStart™ COVID-19 IgM/IgG in IFU-RCLM71-E / Rev. A ACCESS BIO, INC. Page 12 of 19
RCLM-02571
CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
accordance with the authorized labeling. All laboratory personnel using the assay must also
be trained in and be familiar with the interpretation of results of the CareStart™ COVID-19
IgM/IgG.
7. Access Bio, Inc., authorized distributors, and authorized laboratories using the CareStart™
COVID-19 IgM/IgG will ensure that any records associated with this EUA are maintained
until otherwise notified by FDA. Such records will be made available to FDA for inspection
upon request.
a
The letter of authorization refers to, “Laboratories certified under the Clinical Laboratory Improvement
Amendments of 1988 (CLIA), 42 U.S.C. §263a, that meet requirements to perform moderate or high
complexity tests” as “authorized laboratories".
Performance Characteristics
Clinical Agreement
The clinical performance of CareStart™ COVID-19 IgM/IgG was evaluated using
retrospectively collected SARS-CoV-2 serum and plasma samples at 3 sites by 10 operators
in the U.S. A total of 246 samples, 211 plasma (47 positive and 164 pre-COVID) and 35 serum
(17 positive and 18 negative), collected from the U.S were tested in this study. A total of 164
pre-COVID samples were collected before December 2019 in the U.S. All the collected serum
and plasma samples were confirmed by the FDA EUA authorized SARS-CoV-2 RT-PCR
methods as comparators.
All the negative and positive samples were tested in a blinded fashion. Each sample was
assigned with a unique subject identification code during collection and randomized prior to the
testing. The expected results of the samples were completely blinded to the operators in this
study. All the samples were tested according to the CareStart™ COVID-19 IgM/IgG testing
procedures.
A total of 246 samples were considered evaluable in this study.
CareStart™ COVID-19 IgM/IgG Performance against the Comparator Methods
For IgG antibody detection, the positive percent agreement (PPA) of CareStart™ COVID-19
IgM/IgG was 96.88% (62/64) (95% CI of 89.30 – 99.13%) and negative percent agreement
(NPA) was 99.45% (181/182) (95% CI of 96.95 – 99.90%). For IgM antibody detection, the
PPA was 89.06% (57/64) (95% CI of 79.10 - 94.60%) and NPA was 99.45% (181/182) (95%
CI 96.95 - 99.90%).
The overall PPA (either IgG positive or IgM positive counted as positive) was 98.44% (63/64)
(95% CI of 91.67 – 99.72%) and overall NPA was 98.90% (180/182) (95% CI 96.08 – 99.70%).
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CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
IgG results stratified by days post-onset of symptoms
Days from Total number of
Non-reactive Reactive PPA 95% CI
Symptom Onset samples
0-7 - - - - -
8 - 14 1 0 1 100% (1/1) 20.65 – 100%
≥ 15 62 2 60 96.77% (60/62) 88.98 – 99.11%
Unknown 1 0 1 100% (1/1) 20.65 - 100.01%
IgM results stratified by days post-onset of symptoms
Days from Total number of
Non-reactive Reactive PPA 95% CI
Symptom Onset samples
0-7 - - - - -
8 - 14 1 0 1 100% (1/1) 20.65 - 100.01%
≥ 15 62 7 55 88.71% (55/62) 78.48 - 94.42%
Unknown 1 0 1 100% (1/1) 20.65 - 100.01%
Independent Clinical Agreement Validation
The CareStart™ COVID-19 IgM/IgG from Access Bio was tested on Jun 2, 2020 at the Frederick
National Laboratory for Cancer Research (FNLCR) sponsored by the National Cancer Institute
(NCI). The test was validated against a panel of previously frozen samples consisting of 30
SARS-CoV-2 antibody-positive serum samples and 80 antibody-negative serum and plasma
samples. Each of the 30 antibody-positive samples was confirmed with a nucleic acid
amplification test (NAAT) and both IgM and IgG antibodies were confirmed to be present in all
30 samples. The presence of antibodies in the samples was confirmed by several orthogonal
methods prior to testing with the CareStart™ COVID-19 IgM/IgG. The presence of IgM and IgG
antibodies specifically was confirmed by one or more comparator methods. Antibody-positive
samples were selected at different antibody titers.
All antibody-negative samples were collected prior to 2020 and include: i) Seventy (70) samples
selected without regard to clinical status, “Negatives” and ii) Ten (10) samples selected from
banked serum from HIV+ patients, “HIV+”. Testing was performed by one operator using one
lot of the CareStart™ COVID-19 lgM/lgG. Confidence intervals for sensitivity and specificity were
calculated per a score method described in CLSI EP12-A2 (2008).
For the evaluation of cross-reactivity with HIV+, it was determined whether an increased false
positive rate among antibody-negative samples with HIV was statistically higher than the false
positive rate among antibody-negative samples without HIV (for this, a confidence interval for
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CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
the difference in false positive rates was calculated per a score method described by Altman).
The results and data analysis are shown in the tables below:
Comparator Method Collected pre-2020
Antibody Positive Antibody Negative
CareStartTM IgM+, IgM+, IgM-,
Negative HIV+ Total
COVID-19 IgM/IgG IgG+ IgG- IgG+
IgM+, IgG+ 27 27
IgM+, IgG- 1 0 1
IgM-, IgG+ 3 1 4
IgM-, IgG- 68 10 78
Total 30 70 10 110
Measure Estimate Confidence Interval
IgM Sensitivity 90.0% (27/30) 74.4%; 96.5%
IgM Specificity 98.8% (79/80) 93.3%; 99.8%
IgG Sensitivity 100% (30/30) 88.7%; 100%
IgG Specificity 98.8% (79/80) 93.3%; 99.8%
Combined Sensitivity 100% (30/30) 88.7%; 100%
Combined Specificity 97.5% (78/80) 91.3%; 99.3%
Combined PPV for prevalence = 5.0% 67.8% 35%; 88.4%
Combined NPV for prevalence = 5.0% 100% 99.4%; 100%
Cross-reactivity with HIV+ 0.0% (0/10), not detected -
Important limitations of the study:
1. Samples were not randomly selected, and sensitivity and specificity estimates may not
be indicative of the real-world performance of the device
2. These results are based on serum and plasma samples only and may not be indicative
of performance with other sample types, such as whole blood, including finger stick
blood.
3. Information about anticoagulants used is not known.
4. The number of samples in the panel is a minimally viable sample size that still provides
reasonable estimates and confidence intervals for test performance, and the samples
used may not be representative of the antibody profile observed in patient populations.
Cross-Reactivity (Exclusivity)
The cross-reactivity study was conducted by testing a total of 87 plasma or serum samples,
including 14 non-SARS-CoV-2 pathogens and one (1) autoantibody. All the plasma and serum
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CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
samples tested as negative showed no cross-reactivity and resulted in 100% agreement
between CareStart™ COVID-19 IgM/IgG test result and the expected result as presented in
the table below:
Test results (# of positive / # of replicate)
Samples Sample number and type
IgM Results IgG Results
Anti-Influenza A 5 plasma 0/5 0/5
Anti-Influenza B 5 plasma 0/5 0/5
Anti-HCV 8 plasma, 2 serum 0/10 0/10
Anti-HBV 5 serum 0/5 0/5
Anti-229E (alpha coronavirus) 3 plasma 0/3 0/3
Anti-NL63 (alpha coronavirus) 7 plasma 0/7 0/7
Anti-OC43 (beta coronavirus) 9 plasma 0/9 0/9
Anti-HKU1 (beta coronavirus) 5 plasma 0/5 0/5
Antinuclear antibodies (ANA) 5 serum 0/5 0/5
Anti-respiratory syncytial virus 1 plasma, 5 serum 0/6 0/6
Anti-HIV 10 plasma 0/10 0/10
Anti-Dengue virus 5 plasma 0/5 0/5
Anti-T. pallidum (Syphilis) 5 serum 0/5 0/5
Anti-Rhinovirus 2 plasma 0/2 0/2
Anti-Hepatitis B 5 plasma 0/5 0/5
Interfering Substances
To assess substances with the potential to interfere with the performance of the CareStart™
COVID-19 IgM/IgG, SARS-CoV-2 IgM, IgG positive, and negative samples were tested with
the addition of potentially interfering substances. The CareStart™ COVID-19 IgM/IgG test
performance was not affected by any of eight potentially interfering substances tested.
• Acetaminophen • HAMA
• Acetylsalicylic acid • Hemoglobin
• Albendazole • Ibuprofen
• Chloroquine diphosphate • Rifampicin
The interfering effects of biotin concentrations ranging between 10 ng/ml and 100 µg/ml were
tested in a separate study. Biotin concentrations up to 2.5 µg/ml did not lead to false results.
Biotin concentrations >5 µg/ml can cause false-negative IgM results with the CareStart™
COVID-19 IgM/IgG. None of the IgG positive samples tested produced false negative in all
biotin concentrations tested.
IFU-RCLM71-E / Rev. A ACCESS BIO, INC. Page 16 of 19RCLM-02571
CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
Class Specificity
The CareStart™ COVID-19 IgM/IgG was evaluated to determine that the assay accurately
detects each SARS-CoV-2 IgM and IgG antibody class on its corresponding test lines. A total
of five (5) IgM and IgG positive serum samples were treated with DTT to determine class
specificity of the test. All samples treated with DTT showed no visible IgM line with the
CareStart™ COVID-19 IgM/IgG, whereas the IgG results were not affected by DTT treatment.
IgM and IgG results after DTT treatment showed 100% agreement to the expected results.
Matrix Equivalency
The matrix equivalency study was performed by spiking SARS-CoV-2 IgM/IgG positive sample
into negative sample matrices for serum, venous whole blood, and plasma using different
anticoagulants. All testing matrices were collected from the same donor and a total of five
donors were evaluated in CareStart™ COVID-19 IgM/IgG. The venous whole blood samples
were collected from each individual in four different containers to prepare serum (no
anticoagulant), and three matrices each of venous whole blood (sodium citrate, sodium heparin,
and dipotassium EDTA) and plasma (sodium citrate, sodium heparin, and dipotassium EDTA).
To prepare positive sample panels, each sample matrix was spiked with SARS-CoV-2 IgM/IgG
positive serum sample at low positive and moderate positive levels and randomized for testing.
The samples were tested in duplicate with the CareStart™ COVID-19 IgM/IgG. All the test
results of seven different matrices from the individual showed 100% agreement to the expected
results.
Test results (# of positive / # of replicate (% agreement))
Sample type LP results MP results Negative results
IgM IgG IgM IgG IgM IgG
Venous whole blood 10/10 10/10 10/10 10/10 0/10 0/10
(EDTA) (100%) (100%) (100%) (100%) (100%) (100%)
Venous whole blood 10/10 10/10 10/10 10/10 0/10 0/10
(Heparin) (100%) (100%) (100%) (100%) (100%) (100%)
Venous whole blood 10/10 10/10 10/10 10/10 0/10 0/10
(Citrate) (100%) (100%) (100%) (100%) (100%) (100%)
Plasma 10/10 10/10 10/10 10/10 0/10 0/10
(EDTA) (100%) (100%) (100%) (100%) (100%) (100%)
Plasma 10/10 10/10 10/10 10/10 0/10 0/10
(Heparin) (100%) (100%) (100%) (100%) (100%) (100%)
Plasma 10/10 10/10 10/10 10/10 0/10 0/10
(Citrate) (100%) (100%) (100%) (100%) (100%) (100%)
10/10 10/10 10/10 10/10 0/10 0/10
Serum
(100%) (100%) (100%) (100%) (100%) (100%)
IFU-RCLM71-E / Rev. A ACCESS BIO, INC. Page 17 of 19RCLM-02571 CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab Technical Support For questions, or to report a problem, please call Technical Support at +1-888-898-1270 (Available Hours: Mon. to Fri.: 8 a.m. – 5 p.m.) or TShelp@accessbio.net (24/7 available). Test system problems may also be reported to the FDA using the MedWatch reporting system (phone: 1-800 FDA-1088; fax: 1-800 FDA-1078: or http://www.fda.gov/medwatch). IFU-RCLM71-E / Rev. A ACCESS BIO, INC. Page 18 of 19
RCLM-02571
CareStartTM COVID-19 IgM/IgG Rapid Diagnostic Test for Detection of SARS-CoV-2 IgM/IgG Ab
Description of Symbols
Symbol Descriptions Symbol Descriptions
In vitro diagnostic medical device Catalog number
Indicates a medical device that is intended to be Indicates the manufacturer’s catalog number so
used as an in vitro diagnostic medical device. that the medical device can be identified.
Consult instructions for use Caution
Indicates the need for the user to consult the Indicates the need for the user to consult the
instructions for use. instructions for use for important cautionary
information such as warnings and precautions
that cannot, for a variety of reasons, be
presented on the medical device itself.
Manufacturer Date of manufacture
Indicates the medical device manufacturer. Indicates the date when the medical device was
manufactured.
Batch code Temperature limit
Indicates the manufacturer’s batch code so that Indicates the temperature limits to which the
the batch or lot can be identified. medical device can be safely exposed.
Do not re-use Do not use if the package is damaged
Indicates a medical device that is intended for Indicates a medical device that should not be
one use, or uses on a single patient during a used if the package has been damaged or
single procedure. opened.
Use by date Contains sufficient for tests
Indicates the date after which the medical Indicates the total number of IVD tests that can
device is not to be used. be performed with the IVD.
Prescription-only
Manufactured by: Manufactured for:
Access Bio, Inc. Intrivo Diagnostics, Inc.
65 Clyde Road, Suite A. 2021 Santa Monica Blvd, #11
Somerset, NJ 08873, USA Santa Monica, CA 90404, USA
Tel: 732-873-4040 Tel: 888-965-0301
Fax: 732-873-4043 Fax: 888-965-0302
Email: info@accessbio.net Email: info@intrivo.com
Website: www.accessbio.net Website: www.intrivo.com
Technical Support in the U.S.
Tel: +1-888-898-1270 (Toll Free)
Email: TShelp@accessbio.net
Document number: IFU-RCLM71-E
Revision number: A
Effective date: 2020-07-22
IFU-RCLM71-E / Rev. A ACCESS BIO, INC. Page 19 of 19You can also read
